Quality control in the MRFIT local screening and clinic laboratory.

Quality control was emphasized in the screening and clinic laboratory during the early stages of the trial to cover all aspects of screening, and in the later stages to cover local testing used to monitor the participant in the clinic and to guarantee collection of valid specimens to be shipped to the Central Laboratory. Special attention throughout the trial was focused on techniques for collection of specimens, since it was recognized that analytical results could not be better than the quality of the specimens. Training courses, on-site visits, and newsletters were used to sensitize the staff of the clinic laboratory about the necessity to follow protocol. Any monitoring evidence of carelessness, use of deteriorated supplies, failure to follow safety rules, and deviation from directions in the MRFIT Manual of Operations resulted in memoranda from the Coordinating Center or the Central Laboratory.

Quality control of biochemical data in the Multiple Risk Factor Intervention Trial: Central Laboratory.

The acquisition of quality biochemical data in the MRFIT was enhanced by writing detailed protocols, instituting strict rules for collecting and shipping specimens, setting high goals for analytical performance, using reliable means to transfer data, employing dedicated and competent analysts, and having a director of the Central Laboratory who believed in and enforced an effective quality control system. A Laboratory Quality Control Subcommittee was formed to work with this director in solving laboratory problems, with the Coordinating Center in conducting appropriate monitoring, with the Quality Control Committee in documenting the quality of data and investigating any laboratory problems, and with other committees of the directors and Program Office in responding to any questions raised about laboratory aspects of the trial. All of these efforts culminated in reliable biochemical data.

Individual character of variation in time-series studies of healthy people: II. Differences in values for clinical chemical analytes in serum among demographic groups, by age and sex.

Assessment of the significance of an observed set of serum chemical values for determining a person's state of health requires comparison with a set of defined reference values. We tested the assumption that a reference group of individuals, categorized by age and sex, gives a narrower range of variation than does a larger mixed population. If this were true, the demographic set would be a more sensitive reference than is the customary "normal range" for interpretation of values occurring in the individual. The ratio, R, of intra-personal to inter-personal (group) standard deviations was similar for defined age/sex classes and the overall group for 16 serum constituents. When the "raw" intra-individual variation (biological plus analytical variation) was adjusted to remove the average analytical component, the resulting R was less than 80 for all constituents except creatine kinase, which indicates that these are all particularly strong "discriminators" of individuality. These results imply the need for individual rather than population-based reference ranges, even if the latter are from persons of similar age and the same sex.

Comparison of estimates of long-term analytical variation derived from subject samples and control serum.

Variation in the assays of uniform control serum commonly are assumed to represent day-to-day analytical variation. To test this assumption, we compared the differences between results of serum aliquots assayed immediately for 12 constituents and frozen aliquots accumulated and assayed on a single day with the results of control serum variation from the same period. One aliquot of each weekly sample was stored frozen. Eleven subjects were sampled for 12 weeks. Storage at --20 degrees C for 15 weeks had a mild destructive effect on two enzymes in serum. The control serum data revealed significant linear trends in magnesium (upwards) and alkaline phosphatase (downwards) that substantially increased the respective variances. In the other 10 constituents tested, comparison of variances indicated that long-term (weeks) variation in control serum assays is similar to the difference of variation between aliquots assayed immediately and those frozen and assayed at the same time. For these constituents, this finding justifies the use of control serum to estimate long term analytical variation.

Interlaboratory comparison of enzymatic methods for serum glucose determination.

This report describes an interlaboratory comparison of enzymatic serum glucose methods as currently applied in several instrumental adaptations. Four spectrophotometric, hexokinase-based methods used with the Du Pont "aca," the Abbott "Bichromatic Analyzer," the Aminco "Rotochem," and the Technicon "AutoAnalyzer ll" were compared with glucose oxidase-based methods as used with the Beckman "Glucose Analyzer" and the "AutoAnalyzer ll." We analyzed both normal samples and samples that contained potential interfering substances or were otherwise abnormal. Although all methods were satisfactorily precise, methodological bias was noted in several cases, particularly with abnormal specimens. The hexokinase-based methods were generally more variable. The most consistent data were obtained from the two glucose oxidase methods and the Du Pont aca. Results of this study comprise part of the background information required for development of an accurate glucose reference method under the auspices of the AACC Standards Committee.